The misfolding of the cellular prion protein (PrPC) causes infectious neurodegenerative conditions called prion diseases. In the framework of the ERC-funded study “The Prion Protein in Health and Disease” the team of Adriano Aguzzi has discovered that antibodies against the flexible tail (FT) of PrPC are neuroprotective against prion pathologies. Here we propose to clone and express such antibodies from humans and to develop them as antiprion therapeutics. The principal investigator has founded a company (www.Mabylon.com) which has established a high-yield method for cloning paired heavy and light chains from human memory B cells. The proposed research program will identify rare anti-FT immunoreactive individuals among large populations by high-throughput screening. The clinical information of the selected individuals will help to identify antibodies from persons devoid of pathologies that may be related to anti-PrPC autoimmunity. Therefore, the human antibodies generated within this program will represent fast-track investigational new drug (IND) candidates with safety profiles superior to those of murine or humanized antibodies. Completion of the proposed activities will lead to the development of therapies against prion diseases, which are currently considered untreatable and invariably fatal.
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